Tiragolumab

Pictured: A scientist looks into a microscope/Taylor Tieden for BioSpace In the oncology space, drug developers are keen to develop cutting-edge solutions—and lay claim to a piece of a market estimated to hit $359.1 billion by 2028. However, most Phase III trials fail to present significant clinical improvements on the standard of care. "Oncology . . . is huge because there are some successes, but there’s still a huge medical need,” Ansbert Gadicke, managing partner at MPM BioImpact, told BioSpace earlier this year. Vlad Vitoc, CEO of the immune-oncology company MAIA Biotechnology, concurred. “These trials are important for the niche patient populations they serve,” he told BioSpace. Vitoc lauded successful recent Phase III trial successes as welcome advancements, noting that they will improve care options for patients beyond what is currently available. Here, we highlight five such trials with game-changing potential for oncology and the potential to influence the current market. 1. BMS Well-Positioned to Compete in First-Line Liver Cancer Market Bristol Myers Squibb is knocking on the door of a liver cancer market currently led by AstraZeneca and Roche. In March, BMS revealed that Opdivo and Yervoy improved survival in patients with untreated advanced hepatocellular carcinoma (HCC) in the Phase III CheckMate-9DW trial compared to the investigator’s choice of therapy sorafenib or lenvatinib. The Checkmate-9DW trial comprised 700 people with untreated advanced HCC given BMS’s combo or sorafenib or lenvatinib. The study hit its primary overall endpoint, with interim analysis showing that patients in the Opdivo and Yervoy arm were living longer than those in the control arm. An FDA approval of the Opdivo/Yervoy combo would position BMS to compete in the first-line liver cancer market alongside Roche and AstraZeneca. Roche's checkpoint inhibitor Tecentriq was approved by the FDA in combination with VEGF inhibitor Avastin in 2020. Two years later, AstraZeneca won approval for Imjudo combined with Imfinzi. 2. Pfizer Seeks Eighth Indication for ADC Adcetris Also last month, Pfizer recorded positive results from a Phase III trial for its Adcetris regimen in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Adcetris—an antibody-drug conjugate (ADC) known as brentuximab vedotin—combined with lenalidomide and rituximab showed “statistically significant and clinically meaningful” improvements in overall survival, the trial’s primary endpoint, compared to lenalidomide and rituximab plus placebo. Adcetris also showed significant improvement in the secondary endpoints of progression-free survival (PFS) and overall response rate (ORR). While full data from the ECHELON-3 trial have not yet been shared, Pfizer said Adcetris’s safety and tolerability were consistent with previous findings recorded with the drug when used to treat patients with refractory or relapsed DLBCL. With these data in hand, Pfizer will engage with the FDA regarding a regulatory submission, according to the press release. An approval would mark the eighth indication for Adcetris, which was initially approved in 2011. 3. Asieris Data Spark Hope for Non-Surgical HSIL Treatment There could soon be a non-surgical option for cervical high-grade squamous intraepithelial lesions (HSIL). On March 18, Chinese biopharma Asieris Pharmaceuticals reported that treatment with its cold light photodynamic drug-device combination APL-1702 demonstrated significant efficacy in a Phase III trial, with advancements in high-risk HPV16 and HPV18 clearance rates. Patients treated with APL-1702 showed a statistically significant improvement of 89.4% compared to the placebo control group, Asieris stated in its announcement. The product had a “good” safety profile, according to the company. The trial included 402 eligible patients from across China, Germany and the Netherlands, among other countries. Cervical cancer is the fourth most common cancer in women. Its primary cause is human papillomavirus infection, which causes cervical lesions. Experts project that by 2030, around 16 million people will have HSIL worldwide. 4. Novocure Clocks Positive Data in Brain Metastases from NSCLC An innovative treatment is showing promise in treating brain metastases from NSCLC. Last month, Swiss biotech Novocure reported its Tumor Treating Fields (TTFields) therapy met the primary endpoint in the Phase III METIS clinical trial, demonstrating a statistically significant improvement in time to intracranial progression when combined with supportive care compared to supportive care alone. TTFields uses electric fields that act via many different mechanisms to kill cancer cells. The trial consisted of 298 adult patients with up to 10 brain metastases from NSCLC following stereotactic radiosurgery who received either TTFields or supportive care, including treatments with steroids, anti-coagulants, anti-epileptic drugs, pain control and nausea control. If a second intracranial progression was confirmed, patients were allowed to cross over to the experimental arm. Treatment with the therapy was well-tolerated, with sustained quality of life and neurocognitive functions, according to Novocure. TTFields was first approved by the FDA in 2011 for the treatment of recurrent glioblastoma and Novocure CMO Nicolas Leupin said the company continues to explore the capabilities of this therapy in a variety of solid tumor types. “At Novocure, we pursue aggressive, difficult to treat cancers because we are passionate about helping patients and we believe in the science of TTFields therapy,” Leupin told Biospace. 5. Roche Reports Phase III TIGIT Win Finally, in January, Roche subsidiary Genentech posted positive Phase III data for its anti-TIGIT immunotherapy tiragolumab when used in combination with Tecentriq and chemotherapy. The SKYSCRAPER-08 study, one of seven Phase III trials ongoing for tiragolumab, enrolled 461 patients with esophageal squamous cell carcinoma (ESCC) from Asian countries randomized into a treatment arm and control arm. Tiragolumab combined with Tecentriq and chemotherapy improved PFS compared to chemo alone. The anti-TIGIT market has been a challenging one to crack, with other key players failing to meet their targets. Novartis ended its partnership with BeiGene for an anti-TIGIT therapy in non-small cell lung cancer (NSCLC) last year, taking a $300 million loss. Merck’s Keytruda plus anti-TIGIT vibostolimab also failed to meet the primary endpoints in a Phase II NSCLC study in 2023. Gilead and Arcus Biosciences have fared better, recording “encouraging results” in a Phase II trial for Giliead’s domvanalimab, an anti-TIGIT antibody, used in combination with Arcus’s anti-PD-1asset zimberelimab and chemo, according to the partners’ November 2023 announcement. Further growth in the anti-TIGIT market is anticipated, with more than 40 anti-TIGIT antibodies in clinical trials around the world. Nsisong Asanga is a physician, field epidemiologist, and freelance health writer. You can reach her on LinkedIn.

Pictured: Roche's building in Shanghai, China/iStock, Robert Way Roche subsidiary Chugai Pharmaceutical on Thursday unveiled results from the Phase III LUMINESCE study, showing that its IL-6 inhibitor Enspryng (satralizumab) could significantly improve generalized myasthenia gravis symptoms that affect daily life. However, the biotech was unsatisfied with the magnitude of Enspryng’s effects, noting in the announcement that “the results did not reach our expectations on the degree of clinical benefit.” In terms of safety, LUMINESCE found that Enspryng was well-tolerated when used to treat generalized myasthenia gravis (gMG), with an adverse event pro was consistent with what had been established in trials in neuromyelitis optica spectrum disorder (NMOSD). Roche and Chugai did not provide specific data in their announcement but promised to present detailed results at the upcoming American Academy of Neurology Annual Meeting on April 15 in Denver, Colorado. The companies also did not detail their future plans for Enspryng in gMG, a chronic autoimmune disorder in which antibodies destroy communication between nerves and muscle, causing weakness of the skeletal muscles. Designed to be delivered via subcutaneous Injections, Enspryng is a recombinant humanized monoclonal antibody that targets the IL-6 cytokine. According to its label, Enspryng’s exact mechanism of action is still unknown, though it is thought to Interfere with IL-6 signaling and the inflammatory cascade. Enspryng won the FDA’s approval in August 2020 for the treatment of NMOSD patients positive for the aquaporin-4 antibody. Thursday’s readout does not affect Enspryng’s approval in NMOSD, according to the companies’ announcement. Roche and Chugai will also continue to develop Enspryng in other inflammatory and neurological autoimmune indications, including myelin oligodendrocyte glycoprotein-associated disorder, thyroid eye disease and autoimmune encephalitis. LUMINESCE’s disappointing data buck Roche’s clinical winning streak in recent months. Last week, the pharma announced during a neurology-focused investor event that its investigational Alzheimer’s disease therapy trontinemab cleared a Phase Ib/II study, demonstrating rapid and robust reduction in amyloid plaque levels. Trontinemab, developed using Roche’s proprietary Brainshuttle technology, penetrates the blood-brain barrier reaching high levels of distribution throughout the central nervous system. Earlier this month, Roche’s Alnylam-partnered RNAi therapeutic zilbesiran aced its Phase II study, eliciting a significant drop in 24-hour mean systolic blood pressure. Roche also recently reported several Phase III victories, including one for its asthma drug Xolair (omalizumab) in food allergies and its anti-TIGIT immunotherapy tiragolumab in esophageal squamous cell carcinoma. In December 2023, the pharma announced that its orally available PI3Kα inhibitor inavolisib significantly improved progression-free survival in PIK3CA-mutated, HER2-negative breast cancer when used with palbociclib and fulvestrant in the first-line setting. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.